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I learn that the nerves from the Peripheral Nervous System can carry signals from and to other organs of the body.
I'm wondering if A Single Nerve carries
1) Only chemical signals
2) Only physical signals
3) Both of them at the same time
4) It can occur either of the case below, either (1), (2), or (3) Thank you!
When you say "nerve" this refers to a bundle of axons from many different neurons, but I suspect what you actually mean is a single neuron.
Synapses occur at the ends of axons. Almost all axons branch to some degree, so there are many of these endings, and they fairly exclusively end in chemical synapses.
However, the actual propagation of the signal down the axon is electrical.
Electrical synapses ("gap junctions") also occur in vertebrate nervous systems, but they do not necessarily involve the ends of axons contacting dendrites of other cells. Rather, electrical synapses tend to be between dendrites of different cells, or between a dendrite and the somatic region of another cell, or between axons of two different cells.
The neurons that make electrical synapses also typically make chemical synapses in other places - sometimes they make these electrical synapses with the same cells they make chemical synapses with.
Note that these rules are different in invertebrates, and in general the distinction between axons and dendrites in invertebrates is more complicated.
There are other places besides the CNS with gap junctions/electrical synapses as well, including in the enteric nervous system and in the heart.
Draguhn, A., Traub, R. D., Schmitz, D., & Jefferys, J. G. R. (1998). Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro. Nature, 394(6689), 189.
Galarreta, M., & Hestrin, S. (2001). Electrical synapses between GABA-releasing interneurons. Nature Reviews Neuroscience, 2(6), 425.
Traub, R. D., Bibbig, R., Piechotta, A., Draguhn, R., & Schmitz, D. (2001). Synaptic and nonsynaptic contributions to giant IPSPs and ectopic spikes induced by 4-aminopyridine in the hippocampus in vitro. Journal of Neurophysiology, 85(3), 1246-1256.
Neurons are cells that are specialized to receive, propagate, and transmit electrochemical impulses. In the human brain alone, there are over eighty billion neurons. Neurons are diverse with respect to morphology and function. Thus, not all neurons correspond to the stereotypical motor neuron with dendrites and myelinated axons that conduct action potentials. Some neurons such as photoreceptor cells, for example, do not have myelinated axons that conduct action potentials. Other unipolar neurons found in invertebrates do not even have distinguishing processes such as dendrites. Moreover, the distinctions based on function between neurons and other cells such as cardiac and muscle cells are not helpful. Thus, the fundamental difference between a neuron and a nonneuronal cell is a matter of degree.
Another major class of cells found in the nervous system are glial cells. These cells are only recently beginning to receive attention from neurobiologists for being involved not just in nourishment and support of neurons, but also in modulating synapses. For example, Schwann cells, which are a type of glial cell found in the peripheral nervous system, modulate synaptic connections between presynaptic terminals of motor neuron endplates and muscle fibers at neuromuscular junctions.
One prominent characteristic of many neurons is excitability. Neurons generate electrical impulses or changes in voltage of two types: graded potentials and action potentials. Graded potentials occur when the membrane potential depolarizes and hyperpolarizes in a graded fashion relative to the amount of stimulus that is applied to the neuron. An action potential on the other hand is an all-or-none electrical impulse. Despite being slower than graded potentials, action potentials have the advantage of traveling long distances in axons with little or no decrement. Much of the current knowledge of action potentials comes from squid axon experiments by Sir Alan Lloyd Hodgkin and Sir Andrew Huxley.
The Hodgkin–Huxley model of an action potential in the squid giant axon has been the basis for much of the current understanding of the ionic bases of action potentials. Briefly, the model states that the generation of an action potential is determined by two ions: Na + and K + . An action potential can be divided into several sequential phases: threshold, rising phase, falling phase, undershoot phase, and recovery. Following several local graded depolarizations of the membrane potential, the threshold of excitation is reached, voltage-gated sodium channels are activated, which leads to an influx of Na + ions. As Na + ions enter the cell, the membrane potential is further depolarized, and more voltage-gated sodium channels are activated. Such a process is also known as a positive feedback loop. As the rising phase reaches its peak, voltage-gated Na + channels are inactivated whereas voltage-gated K + channels are activated, resulting in a net outward movement of K + ions, which re-polarizes the membrane potential towards the resting membrane potential. Repolarization of the membrane potential continues, resulting in an undershoot phase or absolute refractory period. The undershoot phase occurs because unlike voltage-gated sodium channels, voltage-gated potassium channels inactivate much more slowly. Nevertheless, as more voltage-gated K + channels become inactivated, the membrane potential recovers to its normal resting steady state..
Neurons communicate with one another via synapses. Synapses are specialized junctions between two cells in close apposition to one another. In a synapse, the neuron that sends the signal is the presynaptic neuron and the target cell receives that signal is the postsynaptic neuron or cell. Synapses can be either electrical or chemical. Electrical synapses are characterized by the formation of gap junctions that allow ions and other organic compound to instantaneously pass from one cell to another.  Chemical synapses are characterized by the presynaptic release of neurotransmitters that diffuse across a synaptic cleft to bind with postsynaptic receptors. A neurotransmitter is a chemical messenger that is synthesized within neurons themselves and released by these same neurons to communicate with their postsynaptic target cells. A receptor is a transmembrane protein molecule that a neurotransmitter or drug binds. Chemical synapses are slower than electrical synapses.
After neurotransmitters are synthesized, they are packaged and stored in vesicles. These vesicles are pooled together in terminal boutons of the presynaptic neuron. When there is a change in voltage in the terminal bouton, voltage-gated calcium channels embedded in the membranes of these boutons become activated. These allow Ca 2+ ions to diffuse through these channels and bind with synaptic vesicles within the terminal boutons. Once bounded with Ca 2+ , the vesicles dock and fuse with the presynaptic membrane, and release neurotransmitters into the synaptic cleft by a process known as exocytosis. The neurotransmitters then diffuse across the synaptic cleft and bind to postsynaptic receptors embedded on the postsynaptic membrane of another neuron. There are two families of receptors: ionotropic and metabotropic receptors. Ionotropic receptors are a combination of a receptor and an ion channel. When ionotropic receptors are activated, certain ion species such as Na + to enter the postsynaptic neuron, which depolarizes the postsynaptic membrane. If more of the same type of postsynaptic receptors are activated, then more Na + will enter the postsynaptic membrane and depolarize cell. Metabotropic receptors on the other hand activate second messenger cascade systems that result in the opening of ion channel located some place else on the same postsynaptic membrane. Although slower than ionotropic receptors that function as on-and-off switches, metabotropic receptors have the advantage of changing the cell's responsiveness to ions and other metabolites, examples being gamma amino-butyric acid (inhibitory transmitter), glutamic acid (excitatory transmitter), dopamine, norepinephrine, epinephrine, melanin, serotonin, melatonin, endorphins, dynorphins, nociceptin, and substance P.
Postsynaptic depolarizations can either transmit excitatory or inhibitory neurotransmitters. Those that release excitatory vesicles are referred to as excitatory postsynaptic potential (EPSP). Alternatively, inhibitory vesicles stimulate postsynaptic receptors such as to allow Cl − ions to enter the cell or K + ions to leave the cell, which results in an inhibitory postsynaptic potential (IPSP). If the EPSP is dominant, the threshold of excitation in the postsynaptic neuron may be reached, resulting in the generation of an action potential in the neuron(s) in turn postsynaptic to it, propagating the signal.
Synaptic plasticity is the process whereby strengths of synaptic connections are altered. For example, long-term changes in synaptic connection may result in more postsynaptic receptors being embedded in the postsynaptic membrane, resulting in the strengthening of the synapse. Synaptic plasticity is also found to be the neural mechanism that underlies learning and memory.  The basic properties, activity and regulation of membrane currents, synaptic transmission and synaptic plasticity, neurotransmission, neuroregensis, synaptogenesis and ion channels of cells are a few other fields studied by cellular neuroscientists.   Tissue, cellular and subcellular anatomy are studied to provide insight into mental retardation at the Mental Retardation Research Center MRRC Cellular Neuroscience Core.  Journals such as Frontiers in Cellular Neuroscience and Molecular and Cellular Neuroscience are published regarding cellular neuroscientific topics. [ citation needed ]
An electrical synapse transmits information through local currents. This type of synapse also has no synaptic delay (how long it takes a synaptic connection to form).
This type of synapse is quite opposite to a chemical synapse. That means electrical synapses are symmetrical, bidirectional, and have low plasticity. That last characteristic means they always send information in the exact same way. Thus, when an action potential activates in a neuron, it replicates in the next neuron.
Sensory Neurons - Move signals from the outer portion of the body to the central nervous system (brain/spinal cord)
Interneurons - Links various neurons together between the brain and spinal cord.
An Integrative Theory of Prefrontal Cortex Function
Earl K. Miller Jonathan D. Cohen
Vol. 24, 2001
▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we . Read More
Figure 1: Schematic diagram of some of the extrinsic and intrinsic connections of the prefrontal cortex. The partial convergence of inputs from many brain systems and internal connections of the pref.
Figure 2: Schematic diagram illustrating our suggested role for the PF cortex in cognitive control. Shown are processing units representing cues such as sensory inputs, current motivational state, me.
Figure 3: (A) Shown is the activity of four single prefrontal (PF) neurons when each of two objects, on different trials, instructed either a saccade to the right or a saccade to the left. The lines .
Figure 4: Schematic of the Stroop model. Circles represent processing units, corresponding to a population of neurons assumed to code a given piece of information. Lines represent connections between.
Figure 5: Time course of fMRI activity in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) during two phases of a trial in the instructed Stroop task. During the instruction.
There are six chief findings in this study. (1) The electrophysiological properties of slowly and rapidly adapting neurons in organ VS-3 correlate with their staining intensity for AChE. The electrophysiological type of each neuron can therefore be identified histochemically, without the need for intracellular recording. (2) All sensory neurons, in slit sensilla, tactile hairs, trichobothria, and internal joint receptors, are supplied by several GABA-LIR fibers of three different morphological types. These fibers form numerous varicosities at the dendritic, somatic, and initial axon regions of the sensory neurons, most densely over the latter zone. (3) The neurons in all four sensillum types investigated reveal punctate SYN-LIR. The distribution of such SYN-LIR is similar to the distribution of GABA-LIR sites across these neurons. (4) Double labeling shows that GABA-LIR and SYN-LIR widely colocalize at all sensory neurons investigated here. Some SYN-LIR puncta are not GABA-LIR, however, indicating that they use (an)other neurotransmitter(s). (5) Three-dimensional reconstruction of the two mechanosensory neurons in a slit of organ VS-3 shows that all synapses originate from fine fibers running in parallel to the sensory neurons. Postsynaptic elements are mechanosensory neurons, glial cells, and fine fibers themselves. At least two different types of synaptic terminals are distinguishable with different sizes of synaptic vesicles, suggesting they release different neurotransmitters. The distribution of GABA-LIR and SYN-LIR has a pattern similar to the fine presynaptic fibers seen in EM reconstruction. (6) Degeneration studies are consistent with the efferent origin of the fine fibers from GABA-LIR somata in the CNS.
It is not clear why the mechanosensory neurons express AChE activity or why they do so differentially. The staining intensity for AChE is not a size or volume effect. As demonstrated previously (Fabian and Seyfarth, 1997), many of the two neurons in a pair are of similar size but still show the clear difference in staining. Moreover, the darker neuron (Type a) is not always the smaller one of a pair. Only in the two neurons associated with slit 2, however, are the size, staining intensity, and mode of adaptation correlated consistently. Although the neurons may be cholinergic, insofar as they express choline acetyltransferase-like immunoreactivity (Fabian and Seyfarth, 1997) and their terminals may therefore have presynaptic cholinoceptors (Wonnacott, 1997), these should lie far away, in the CNS. It is possible that a large pool of AChE is stored differentially in one of the somata, but it may also be that the AChE reflects either nonsynaptic or even noncatalytic functions of AChE (Massoulié et al., 1993) not directly related to the particular rate of electrophysiological adaptation behavior of each neuron type.
There is good reason to suggest that punctate SYN-LIR at the neurons in all sensilla types investigated here represents the distribution of spider synapsin at presynaptic sites. The specificity of antibody binding has been established previously (Fabian-Fine et al., 1999). Furthermore, our present study shows that all sensory neurons are supplied by GABA-LIR fibers that form numerous varicosities onto the mechanoreceptors. The specificity of the GABA-antibody binding in spider tissue is confirmed by the absence of immunostaining in control preparations and by the presence of characteristically arranged GABA-LIR neurons in the subesophegeal ganglion. The fidelity of colocalization between the SYN-LIR and GABA-LIR patterns endorses the specificity of immunostaining in each. Furthermore, the staining pattern of both antibodies corresponds, in turn, with the general pattern of synapses reconstructed from serial EM. This suggests that some SYN-LIR sites at the neurons do indeed contain GABA and may therefore be GABAergic. Although there has been fine structural evidence for some time that sensory neurons in arachnids receive peripheral synaptic input (Foelix, 1975, 1985), this is the first demonstration of the distribution of GABA-LIR fibers.
Efferent inhibitory pathways to mechanosensory neurons
GABA mediates widespread inhibitory mechanisms in the nervous system (Roberts et al., 1976) and is widely distributed at the peripheral synapses of efferent innervations in various invertebrates. Examples include the neuromuscular junctions of nematodes (Johnson and Stretton, 1987), insects (Usherwood and Grundfest, 1965), and Crustacea (Kravitz et al., 1963). In addition, peripheral GABAergic innervation of sensory neurons in the crustacean muscle receptor organ (MRO) arises from efferent inhibitory innervation (Bazemore et al., 1957 Kuffler and Edwards, 1958 Elekes and Florey, 1987a), with a mechanism of action that is well investigated and particularly clear (Hagiwara et al., 1960). It does not seem unreasonable, therefore, to propose a similar inhibitory action for the fine GABA-LIR fibers reported here. Based on their ultrastructural investigations of internal joint receptors in spiders, Foelix and Choms (1979) have suggested that peripheral synapses may represent a pathway for central control that could inhibit receptor activity. From our degeneration tests, the origin of the presynaptic fine fibers appears to be central. There do remain, however, a few fine profiles that survive axotomy for longer than 8 hr. Examples are known in a number of other invertebrate nervous systems in which anucleate axons survive intact for long periods of time (for review, see Bittner, 1991). Although we cannot automatically assume the same phenomenon for such profiles in spiders, the only peripherally located neuron somata described are the mechanosensory neurons themselves, for which dye-fills (retrograde, as well as anterograde) show no evidence of axon collateral branches (Seyfarth et al., 1985). GABA immunostaining reveals numerous GABA-LIR perikarya in the subesophageal ganglion, but none in the periphery, and so confirms the efferent origin of these fibers. We therefore propose that the surviving small-fiber profiles seen after nerve section in our preparations are those of central neuron(s) in which degeneration is delayed.
Distribution and differentiation of synaptic contacts
The fine fibers at VS-3 neurons reconstructed from our EM series form linear rows of presynaptic varicosities, with consecutive presynaptic contacts that are concentrated on the initial axon segment. These findings correspond to the ultrastructural description of peripheral synapses at spider internal joint receptors provided previously by Foelix and Choms (1979). Inhibition at such proximal sites is widely seen in neurons (Shepherd, 1990) in which it is strategically located at the site of normal impulse initiation. So far, however, the region of lowest membrane threshold has not been investigated for spider mechanosensory neurons.
We observed three significantly different GABA-LIR fiber types on the basis of their varicosity sizes. This feature shares a similar pattern with the efferent innervation of sensory neurons of the crayfish MRO. After the initial description by Alexandrowicz (1951), Florey and Florey (1955) showed that the sensory neurons in this system are also supplied by three accessory fibers of different sizes they are now known to be GABA-LIR (Elekes and Florey, 1987a).
Three features of the spider’s peripheral innervation are especially significant for synaptic integration. The first is the size of the synaptic vesicles. The two sizes of synaptic vesicle (type 1 and type 2) (Figs. 2, 4) are presumed to contain different neurotransmitters. The smaller of two populations of round vesicles at the peripheral synapses on mechanoreceptors of the crustacean MRO (Nakajima and Reese, 1983) is known to contain GABA (Elekes and Florey, 1987a). We assume that the same is also true for the small vesicles of spider mechanoreceptors, whereas the contents of the large vesicles are not yet known. In the crustacean MRO, the second transmitter is glutamate (Takeuchi and Takeuchi, 1964), and it occurs at synapses with large round vesicles. It remains to be seen, however, whether glutamate is a second transmitter candidate at spider mechanoreceptors. The second feature at spider mechanoreceptors is that varicosities have widely differing sizes. Some varicosities are quite large, with numerous vesicles and multiple presynaptic dense bodies visible from EM series, whereas other varicosities contain few vesicles and have only a single dense body onto the sensory neurons. It seems likely that there are differences in transmitter output corresponding to the differences in the number of presynaptic dense bodies (Atwood and Cooper, 1995). Ultrastructurally, synapses with large synaptic vesicles are primarily small, containing relatively few synaptic vesicles. In comparison, synapses with small synaptic vesicles often extend over large distances, containing numerous vesicles. Differences in the size of the vesicle population presumably reflect differences in the sizes of the SYN-LIR puncta seen by light microscopy. The third feature is that numerous synaptic inputs are received not only by the mechanoreceptors but also form between the inputs themselves. Similar connections also occur between inputs at the stretch receptor neurons of the crayfish MRO (Hirosawa et al., 1981 Elekes and Florey, 1987b).
Assuming that the abundant peripheral synapses we describe include those that are GABAergic and inhibitory, a number of functional roles can be envisaged for the spider’s mechanoreceptors. If such efferent fibers are activated simultaneously with motor fibers innervating nearby leg muscles, inhibition could serve to prevent spurious signals resulting from the spider’s own movements, in much the same way, for instance, as for the neuromast organs of tailed vertebrates (Russell, 1971). Alternatively, a release from inhibition or excitation may increase the sensitivity of a receptor for its optimal stimulus, e.g., substrate vibration for the slit sensilla during courtship or prey localization (Barth, 1985). Given the number of efferent fibers, however, it seems likely that inhibitory interactions are more subtle than we can safely speculate from current evidence. An electrophysiological and pharmacological examination in single, identifiable mechanoreceptors (such as the VS-3 neurons) is now required to clarify the functional role of efferent innervation from GABA-LIR fibers.
Neurons, Action Potentials, and Synapses
Neurons are the basic cellular units which constitute the nervous system. Humans possess approximately 100 billion neurons. An individual neuron generally consists of a soma (cell body), dendrites, and an axon.
The soma contains the cell’s nucleus (where its DNA is stored), and serves to produce proteins necessary for the function of the neuron.
Extending out from the soma are dendrites, which are branch-like structures that form connections with other neurons from which they receive and process electrical signals. Finally, an axon projects out from the other end of the soma and serves in turn to produce and carry an electrical signal to other neurons.
Each neuron usually only contains one axon, although the structure may be branched following the initial projection from the soma (Woodruff, 2019).
The electrical signals carried by axons and transmitted to dendrites are called action potentials. Basically, neurons are electrical devices — they contain channels that allow positive and negative ions to pass from outside to inside the cell or vice versa, which gives rise to an electrical potential with respect to a cell’s membrane (the barrier around the outside of a cell).
By default (when neurons are “at rest”), there is more negative charge on the inside of the cell than outside, giving rise to a resting membrane potential of -70 millivolts. However, this electrical potential is constantly changing in response to inputs from other cells, which cause ions to flow in or out of the cell.
Some of these inputs are “excitatory,” meaning that they make the cell’s membrane potential less negative (for example, by causing positive ions to flow into the cell), while others are “inhibitory,” meaning that they make the cell’s membrane more negative.
If a neuron receives enough excitatory inputs, and not too many inhibitory inputs, its membrane potential will go above what is known as the “action potential threshold” (approximately -50 millivolts), and an action potential will occur.
Electrically, action potentials are brief but dramatic spikes in a neuron’s membrane potential. In fact, neuroscientists often refer to action potentials simply as “spikes".
When a neuron’s membrane potential passes the action potential threshold, it triggers the opening of what are known as voltage-gated sodium channels, which allow positively charged sodium ions to pass into the cell.
This causes the cell’s membrane potential to rapidly become more positive, leading to the spike. This signal then rapidly travels down the length of the neuron’s axon, because the spike itself causes farther down voltage-gated sodium channels to open as well — and so on, and so forth.
Finally, the action potential reaches the end of the axon, and the neuron passes this signal along to other neurons.
Neurons communicate with one another through structures called synapses. A single synapse consists of a presynaptic terminal, a synaptic cleft, and a postsynaptic terminal.
Once an action potential makes it to the end of a neuron’s axon, it reaches the presynaptic terminal, which causes neurotransmitters to be released from the cell. These neurotransmitters are released into the synaptic cleft, a small (20-40nm) gap between the pre- and postsynaptic terminals.
The neurotransmitters then travel across the synaptic cleft and activate neurotransmitter receptors on the postsynaptic terminal. When these receptors are activated, they cause positive or negative ions to flow into the postsynaptic neuron, resulting in excitation or inhibition, respectively.
When neurotransmitters act on receptors to cause positive ions to flow into the postsynaptic neuron, it is called excitation, because the neuron is brought closer to its action potential threshold, and therefore becomes more likely to fire.
Conversely, when neurotransmitters act on receptors to cause negative ions to flow into the postsynaptic neuron, it is called inhibition, because the neuron is brought further away from its action potential threshold, and therefore becomes less likely to fire.
As a result, some neurotransmitters are referred to as excitatory neurotransmitters (since their action on receptors causes excitation), while others are referred to as inhibitory neurotransmitters.
Common excitatory neurotransmitters include glutamate and dopamine common inhibitory neurotransmitters include GABA and glycine. Some neurotransmitters, such as serotonin, can be either excitatory or inhibitory depending on the type of receptor it acts upon.
Key Brain Terms Glossary
action potential: Sometimes called a “spike” or described as a neuron “firing,” an action potential occurs when there is a significant increase in the electrical activity along the membrane of a nerve cell. It is associated with neurons passing electrochemical messages down the axon, releasing neurotransmitters to neighboring cells in the synapse.
addiction: Now commonly called substance use disorder, addiction is a mental health condition where a person’s progressive and chronic use of drugs or alcohol leads to issues with personal relationships, the ability to work, and one’s physical health.
adrenal glands: Located on top of each kidney, these two glands are involved in the body’s response to stress and help regulate growth, blood glucose levels, and the body’s metabolic rate. They receive signals from the brain and secrete several different hormones in response, including cortisol and adrenaline.
adrenaline: Also called epinephrine, this hormone is secreted by the adrenal glands in response to stress and other challenges to the body. The release of adrenaline causes a number of changes throughout the body, including the metabolism of carbohydrates to supply the body’s energy demands and increased arousal or alertness.
allele: One of two or more varying forms of a gene due to genetic mutation. Differing alleles, which can be found at the same spot on a chromosome, produce variation in inherited characteristics such as hair color or blood type. A dominant allele is one whose physiological function—such as making hair blonde—occurs even when only a single copy is present (among the two copies of each gene that everyone inherits from their parents). A recessive allele’s traits only appear when two copies are present.
Alzheimer’s disease: A debilitating form of dementia, this progressive and irreversible neurodegenerative disease results in the development of protein plaques and tangles that damages neurons and interfere with neural signaling, ultimately affecting memory and other important cognitive skills.
amino acid: A type of small organic molecule that has a variety of biological roles but is best known as the “building block” of proteins.
amino acid neurotransmitters: The most prevalent neurotransmitters in the brain, these include glutamate and aspartate, which can increase the electrochemical activity of neurons, as well as glycine and gamma-amino butyric acid (GABA), which inhibit that electrochemical activity.
amygdala: Part of the brain’s limbic system, this primitive brain structure lies deep in the center of the brain and is involved in emotional reactions, such as anger or fear, as well as emotionally charged memories. It also influences behavior such as feeding, sexual interest, and the immediate “fight or flight” stress reaction that helps ensure the person’s needs are met.
amyloid-beta (Aβ) protein: A naturally occurring protein in brain cells. Large, abnormal clumps of this protein form the amyloid plaques that are a physiological hallmark of Alzheimer’s disease. Smaller groupings (oligomers) of Aβ seem more toxic to brain cells and are thought by many researchers to play an important role in the Alzheimer’s disease process.
amyloid plaque: The sticky, abnormal accumulations of amyloid-beta protein aggregate around neurons and synapses in the memory and intellectual centers of the brain, in people with Alzheimer’s. These are sometimes referred to as neuritic plaques or senile plaques. While amyloid plaques have long been considered markers of Alzheimer’s, they are also found to some extent in many cognitively normal elderly people. The plaques’ role in Alzheimer’s neurodegeneration remains unclear.
amyotrophic lateral sclerosis (ALS): Also known as Lou Gehrig’s disease, this neurodegenerative disease results in the death of brain cells that control the muscles.
angiography: A medical imaging technique that allows clinicians to visualize the interior of blood vessels, arteries, veins, and the heart.
animal model: A laboratory animal that—through changes in its diet, exposure to toxins, genetic changes, or other experimental manipulations—mimics specific signs or symptoms of a human disease. Many of the most promising advances in treating brain disorders have come from research on animal models.
antidepressant medication: Classes of drugs that can treat depressive symptoms by affecting the levels of specific neurotransmitters in the brain. One of the most well-known types of antidepressant are selective serotonin reuptake inhibitors.
anxiety: Feelings of intense and persistent worry or fear regarding everyday situations. While some feelings of anxiety are normal, they can be classified as an anxiety disorder when the symptoms start to interfere with daily living.
apoptosis: A form of programmed cell death that occurs as part of normal growth and development. However, in cases of brain disorders or disease, this natural process can be “hijacked,” resulting in the unnecessary death of crucial neurons.
artificial intelligence (AI): computer programs or systems designed to perform tasks that normally require human intelligence, including problem-solving, learning, and decision-making behaviors.
astrocyte: A star-shaped glial cell that supports neurons, by helping to both feed and remove waste from the cell, and otherwise modulates the activity of the neuron. Astrocytes also play critical roles in brain development and the creation of synapses.
attention deficit hyperactivity disorder (ADHD): A neurodevelopmental disorder that affects attention systems and impulse control. While ADHD is primarily known as a pediatric disorder, it also affects adults.
auditory cortex: Part of the brain’s temporal lobe, this region is responsible for hearing. Nerve fibers extending from the inner ear carry nerve impulses generated by sounds into the auditory cortex for interpretation.
autism spectrum disorder (ASD): A neurodevelopmental disorder, with symptoms usually presenting within the first two years of life, characterized by issues of communication, personal interactions, and behavior. It is referred to as a spectrum disorder because of the variety in the type and severity of symptoms observed.
autonomic nervous system: Part of the central nervous system that controls internal organ functions (e.g., blood pressure, respiration, intestinal function, urinary bladder control, perspiration, body temperature). Its actions are mainly involuntary.
axon: A long, single nerve fiber that transmits messages, via electrochemical impulses, from the body of the neuron to dendrites of other neurons, or directly to body tissues such as muscles.
axon terminal: The very end of the axon, where electrochemical signals are passed through the synapse to neighboring cells by means of neurotransmitters and other neurochemicals. A collection of axons coming from, or going to, a specific brain area may be called a white matter fiber tract.
basal ganglia: A group of structures below the cortex involved in motor, cognitive, and emotional functions.
basilar artery: Located at the base of the skull, the basilar artery is a large, specialized blood vessel that supplies oxygenated blood to the brain and nervous system.
biomarkers: A measurable physiological indicator of a biological state or condition. For example, amyloid plaques—as detected on amyloid PET scans—are a biomarker of Alzheimer’s disease. Biomarkers can be used for both diagnostic and therapeutic purposes.
bipolar disorder: Also known as manic depression or manic-depressive disorder, bipolar disorder is characterized by unpredictable changes in mood, as well as energy and activity levels, that can interfere with everyday tasks.
blood-brain barrier: A protective barrier that separates the brain from the blood circulating across the body. The blood-brain barrier is semipermeable, meaning it allows the passage of water as well as molecules like glucose and other amino acids that help promote neural function.
brain-computer interface: A device or program that permits direct or indirect collaboration between the brain and a computer system. For example, a device that harnesses brain signals to control a screen cursor or a prosthetic limb.
brain-derived neurotrophic factor (BDNF): Sometimes referred to as “brain fertilizer,” BDNF is a protein that helps promote the growth, maintenance, and survival of neurons.
brain imaging: Refers to various techniques, such as magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and positron emission tomography (PET), that enable scientists to capture images of brain tissue and structure and to reveal what parts of the brain are associated with behaviors or activities. Structural brain imaging is concerned with identifying the anatomy of the brain and its changes with disease. Functional brain imaging is concerned with identifying the pattern of activity in the brain when people are at rest or when they are performing a task.
brain stem: A primitive part of the brain that connects the brain to the spinal cord, the brain stem controls functions basic to survival, such as heart rate, breathing, digestive processes, and sleeping.
brain tumor: A mass or growth of abnormal cells found in the brain. While people may commonly equate brain tumors with cancer, many tumors are benign—but their location in the brain can still interfere with normal brain function.
brain waves: Rhythmic patterns of neural activity in the central nervous system, brain waves can also be called neural oscillations.
Broca’s area: Discovered by French physician Paul Broca in the late 19 th century, this small region in the left frontal lobe has been linked to speech production.
cell body: Also known as the soma, this central part of the neuron contains the nucleus of the neuron. The axon and dendrites connect to this part of the cell.
central nervous system: The brain and spinal cord constitute the central nervous system and are part of the broader nervous system, which also includes the peripheral nervous system.
central sulcus: The primary groove in the brain’s cerebrum, which separates the frontal lobe in the front of the brain from the parietal and occipital lobes in the rear of the brain.
cerebellar artery: The major blood vessel providing oxygenated blood to the cerebellum.
cerebellum: A brain structure located at the top of the brain stem that coordinates the brain’s instructions for skilled, repetitive movements and helps maintain balance and posture. Research suggests the cerebellum may also play a role, along with the cerebrum, in some emotional and cognitive processes.
cerebral palsy: A developmental disorder resulting from damage to the brain before or during birth, usually characterized by impaired muscle coordination and body movements, but can also include impaired cognition and social behavior.
cerebrospinal fluid (CSF): The clear, colorless liquid found surrounding the brain and spinal cord. This fluid can be analyzed to detect diseases.
cerebrum: The cerebrum is the largest brain structure in humans, accounting for about two-thirds of the brain’s mass and positioned over and around most other brain structures. The cerebrum is divided into left and right hemispheres, as well as specific areas called lobes that are associated with specialized functions.
chromosome: A threadlike structure of nucleotides that carries an organism’s genes or genetic information.
chronic encephalopathy syndrome (CES): Symptoms, including memory issues, depression, and impulsive behavior, that manifest themselves after repeated brain traumas. Over time, CES can result in a diagnosis of chronic traumatic encephalopathy (CTE).
chronic traumatic encephalopathy (CTE): Once known as dementia pugilistica and thought to be confined largely to former boxers, this neurodegenerative disease, with symptoms including impulsivity, memory problems, and depression, affects the brains of individuals who have suffered repeated concussions and traumatic brain injuries.
cochlea: The part of the inner ear that transforms sound vibrations into neural impulses.
cognition: A general term that includes thinking, perceiving, recognizing, conceiving, judging, sensing, reasoning, and imagining.
cognitive neuroscience: The field of study that investigates the biological processes in the brain that underlie attention, memory, and other facets of cognition.
computational neuroscience: An interdisciplinary field of study that uses information processing properties and algorithms to further the study of brain function and behavior.
computed tomography (CT or CAT): An X-ray technique introduced in the early 1970s that enables scientists to take cross-sectional images of the body and brain. CT uses a series of X-ray beams passed through the body to collect information about tissue density, then applies sophisticated computer and mathematical formulas to create an anatomical image from the data.
concussion: A type of mild traumatic brain injury resulting from a blow or hit to the head that causes the brain to move rapidly back and forth inside the skull.
cone: A type of photoreceptor cell responsible for color vision that is found in the retina.
connectome: A detailed map of the myriad neural connections (also called fiber tracts) that make up the brain and nervous system.
consciousness: The state of being aware of one’s feelings and surroundings the totality of one’s thoughts, feelings, and impressions.
corpus callosum: The collection of nerve fibers connecting the two cerebral hemispheres.
cortex: The outer layer of the cerebrum. Sometimes referred to as the cerebral cortex.
cortisol: A steroid hormone produced by the adrenal glands that controls how the body uses fat, protein, carbohydrates, and minerals, and helps reduce inflammation. Cortisol is released in the body’s stress response scientists have found that prolonged exposure to cortisol has damaging effects on the brain.
critical period: A period of development during which an ability or characteristic is thought to be most easily learned or attained.
CRISPR (clustered regularly-interspaced short palindromic repeats): A relatively precise and reliable DNA-editing technique.
deep brain stimulation: A method of treating various neuropsychiatric and neurodegenerative disorders through small, controlled electric shocks administered from a special battery-operated neurostimulation implant. The implant, sometimes called a “brain pacemaker,” is placed within deep brain regions such as the globus pallidus or subthalamus.
deep learning: See machine learning.
default-mode network: The network indicates that the brain remains active even if not involved in a specific task. Even when you are daydreaming, the brain is in an active state.
dementia: General mental deterioration from a previously normal state of cognitive function due to disease or psychological factors. Alzheimer’s disease is one form of dementia.
dendrites: Short nerve fibers that project from a neuron, generally receiving messages from the axons of other neurons and relaying them to the cell’s nucleus.
depression: A mood or affective disorder characterized by sadness and lack of motivation. Depression has been linked to disruptions in one or more of the brain’s neurotransmitter systems, including those related to serotonin and dopamine.
Diagnostic and Statistical Manual of Mental Disorders (DSM): The standard classification manual published by the American Psychiatric Association for mental health professionals to diagnose and treat mental disorders.
diffusion spectrum imaging (DSI): A brain imaging method that detects the movement of water in tissue to help visualize the brain’s white matter. This approach typically allows better resolution than diffusion tensor imaging.
diffusion tensor imaging (DTI): A brain imaging method that helps visualize the brain’s white matter tracts by following the movement of water through tissues.
DNA (deoxyribonucleic acid): The material from which the 46 chromosomes in each cell’s nucleus is formed. DNA contains the codes for the body’s approximately 30,000 genes, governing all aspects of cell growth and inheritance. DNA has a double-helix structure—two intertwined strands resembling a spiraling ladder.
digital phenotyping: The use of data collected from personal electronic devices like smart phones to diagnose and monitor medical and psychiatric conditions.
dominant gene: A gene that almost always results in a specific physical characteristic, for example a disease, even though the patient’s genome possesses only one copy. With a dominant gene, the chance of passing on the gene (and therefore the trait or disease) to children is 50-50 in each pregnancy.
dopamine: A neurotransmitter involved in motivation, learning, pleasure, the control of body movement, and other brain functions.
double helix: The structural arrangement of DNA, which looks something like an immensely long ladder twisted into a helix, or coil. The sides of the “ladder” are formed by a backbone of sugar and phosphate molecules, and the “rungs” consist of nucleotide bases joined weakly in the middle by hydrogen bonds.
Down syndrome: A genetic disorder characterized by intellectual impairment and physical abnormalities that arises from the genome having an extra copy of chromosome 21.
dyslexia: A learning disorder that affects the ability to understand and produce language. It is commonly thought of as a reading disability, although it can affect other aspects of language.
electroencephalography (EEG): A method that measures electrical activity in the brain using small electrodes placed on the scalp.
electroconvulsive therapy (ECT): A therapeutic treatment for depression and other mental illnesses that sends small electric currents over the scalp to trigger a brief seizure.
endocrine system: A system in the body composed of several different glands and organs that secrete hormones.
endorphins: Hormones produced by the brain, in response to pain or stress, to blunt the sensation of pain. Narcotic drugs, such as morphine, imitate the actions of the body’s natural endorphins.
enzyme: A protein that facilitates a biochemical reaction. Organisms could not function if they had no enzymes.
epigenetics: A subset of genetics that focuses on how specific environmental factors can influence where, when, and how a gene is expressed, resulting in variation in the gene’s related traits.
epilepsy: A neurological disorder characterized by abnormal electrical activity in the brain, leading to seizures.
executive function: Higher level cognitive functions, including decision-making and judgment, involved with the control of behavior.
fissure: A groove or indentation observed in the brain.
Fragile X syndrome: A genetic disorder that interferes with brain development, leading to learning disabilities and cognitive impairment, particularly with regards to language.
frontal lobe: The front of the brain’s cerebrum, beneath the forehead. This area of the brain is associated with higher cognitive processes such as decision-making, reasoning, social cognition, and planning, as well as motor control.
frontal operculum: The part of the frontal lobe that sits over the insula.
frontotemporal degeneration (FTD): This is a common type of dementia caused by the loss of neurons in the frontal lobes. This disorder often strikes earlier than Alzheimer’s disease or other forms of dementia, with most patients diagnosed between their late 40’s and early 60’s. It also tends to present with more prominent behavior and social impairments as opposed to memory loss, though memory loss is common in later stages of disease.
functional magnetic resonance imaging (fMRI): A brain imaging technology, based on conventional MRI, that gathers information relating to short-term changes in oxygen consumption by cells in the brain. It typically uses this information to depict the brain areas that become more or less active—and presumably more or less involved—while a subject in the fMRI scanner performs a cognitive task.
gamma-aminobutyric acid (GABA): A neurotransmitter implicated in brain development, muscle control, and reduced stress response.
gene: The basic unit of inheritance. A gene is a distinct section of DNA code in a cell’s chromosome that instructs the cell to make a particular molecule, usually a protein or RNA. Gene defects (genetic mutations) are thought to cause many disorders including brain disorders.
gene expression: The process by which a gene’s nucleotide sequence is transcribed into the form of RNA—often as a prelude to being translated into a protein.
gene mapping: Determining the relative positions of genes on a chromosome and the distance between them.
genome: The complete genetic map for an organism. In humans, this includes about 30,000 genes, more than 15,000 of which relate to functions of the brain.
glia (or glial cells): The supporting cells of the central nervous system. They may contribute to the transmission of nerve impulses and play a critical role in protecting and nourishing neurons.
glioblastoma: An invasive brain tumor made up of glial tissue, blood vessels, and dead neurons.
glioma: A tumor that arises from the brain’s glial tissue.
glucose: A natural sugar that is carried in the blood and is the principal source of energy for the cells of the brain and body.
glymphatic system: The system that helps clear debris from the brain. During sleep, special glial cells called astrocytes form a network of conduits that allow cerebrospinal fluid to flush unwanted and unnecessary proteins out of the brain.
gray matter: The parts of the brain and spinal cord made up primarily of groups of neuron cell bodies (as opposed to white matter, which is composed mainly of myelinated nerve fibers).
gyrus: The ridges on the brain’s outer surface. Plural is gyri.
hemisphere: In brain science, refers to either half of the brain (left or right). The two hemispheres are separated by a deep groove, or fissure, down the center. Some major, specific brain functions are located in one or the other hemisphere. While popular culture suggests that “hemispheric dominance,” or which side of the brain is more active, can help inform how an individual best learns, research does not support this idea.
hippocampus: A primitive brain structure, located deep in the brain, that is critical for memory and learning.
hormone: A chemical released by the body’s endocrine glands (including the adrenal glands), as well as by some tissues. Hormones act on receptors in other parts of the body to influence body functions or behavior.
Huntington’s disease: A neurodegenerative disorder that causes progressive death of neurons in the brain, resulting in severe movement and cognitive problems. The disorder is caused by the mutation of a single gene—and symptoms typically present when an individual is in his or her 30’s or 40’s.
hypothalamus: A small structure located at the base of the brain, where signals from the brain and the body’s hormonal system interact.
in silico: An experimental method to study brain or neural function using computer modeling or computer simulation.
in vitro: An experimental method to study brain or neural function by looking at cells outside a living organism, for example, in a test tube or petri dish.
in vivo: An experimental method allowing scientists to study brain or neural function in a living organism.
induced pluripotent stem cell (iPSC): A cell that has been taken from adult tissue and genetically modified to behave like an embryonic stem cell, with the ability to develop into any type of cell found in the body, including nerve cells.
insula: Sometimes referred to as the insular cortex, this small region of the cerebrum is found deep within the lateral sulcus, and is believed to be involved in consciousness, emotion, and keeping the body in balance.
ions: Atoms or small groups of atoms that carry an electric charge, either positive or negative. When a nerve impulse is fired, ions flow through channels in the membrane of a nerve cell, abruptly changing the voltage across the membrane in that part of the cell. This sets off a chain reaction of similar voltage changes along the cell’s axon to the synapse, where it causes the release of neurotransmitters into the synaptic cleft.
ion channel: A pore in the membrane of a neuron that allows ions to pass through, helping to shape action potentials.
ketamine: A powerful anesthetic drug, originally manufactured for veterinary use, that has been shown to be an effective treatment for major depressive disorder, especially in patients who do not respond well to traditional antidepressant medications.
lesion: An injury, area of disease, or surgical incision to body tissue. Much of what we know about the functions of brain structures or pathways comes from lesion mapping studies, where scientists observe the behavior of people with an injury to a distinct area of the brain or analyze the behavior of a laboratory animal resulting from a lesion made in the brain.
limbic system: A group of evolutionarily older brain structures that encircle the top of the brain stem. The limbic structures play complex roles in emotions, instincts, and appetitive behaviors.
long term potentiation (LTP): The persistent strengthening of a synapse with increased use, thought to underlie learning and memory.
Lou Gehrig’s disease: see amyotrophic lateral sclerosis (ALS)
machine learning: Also referred to as deep learning, machine learning is a type of artificial intelligence algorithm that can learn rules or identify diagnostic criteria from immense data sets of brain imaging or genetic information. These algorithms are becoming more prevalent in scientific research—and are also starting to be incorporated into translational neuroscience research and medical practice.
magnetic resonance imaging (MRI): A non-invasive imaging technology, often used for brain imaging. An MRI scanner includes intensely powerful magnets, typically 10,000 to 40,000 times as strong as the Earth’s magnetic field. These magnets, combined with coils that send electromagnetic pulses into the scanned tissue, induce radio-frequency signals from individual hydrogen atoms within the tissue. The scanner records and processes these signals to create an image of the scanned tissue. MRI scans can depict high resolution images of the entire brain, allowing clinicians to determine if the brain tissue visualized is normal, abnormal, or damaged due to a neurological disorder or trauma. MRI technology has also been adapted to measure brain activity with functional MRI methods.
manic-depressive disorder: See bipolar disorder.
medulla oblongata: The lower part of the brain stem, responsible for life-regulating functions like breathing and heart rate.
melatonin: A hormone that is secreted by the pineal gland in the brain in response to the daily light-dark cycle, influencing the body’s sleep-wake cycle.
memory: The encoding and storage of information, in a way that allows it to be retrieved later. In the brain, memory involves integrated systems of neurons in diverse brain areas, each of which handles individual memory-related tasks. Memory can be categorized into two distinct types, each with its own corresponding brain areas. Memory about people, places, and things that one has experienced directly or otherwise learned about is referred to as explicit or declarative memory and is highly dependent upon the hippocampus and temporal lobe. Memory about motor skills and perceptual strategies is known as implicit or procedural memory and involves the cerebellum, the amygdala, and specific pathways related to the particular skill (e.g., riding a bicycle would involve the motor cortex).
mental health: Referring to one’s psychological, emotional, and social well-being.
mesolimbic circuit: See reward/reinforcement brain network.
mesolimbic pathway: A specialized brain circuit implicated in the processing of risk and reward information.
metabolize: To break down or build up biochemical elements in the body, effecting a change in body tissue. For example, neurons and other brain cells metabolize glucose, a blood sugar, to derive energy for transmitting nerve impulses.
microbiota: The community of various microorganisms found in the digestive tract. Scientists are now learning that microbes found in the microbiota can influence brain development, mood, and behavior.
microglia: A small, specialized glial cell that operates as the first line of immune defense in the central nervous system.
midbrain: Also referred to as the mesencephalon, the midbrain is a small part of the brain stem that plays an important role in movement as well as auditory and visual processing.
minimally conscious state: A disorder of consciousness, often caused by stroke, head injury, or loss of blood flow to the brain, in which an individual maintains partial conscious awareness, but may have great difficulty in communicating with, or understanding, other people.
molecular biology: The study of the structure and function of cells at the molecular level and how these molecules influence behavior and disease processes. Molecular biology emerged as a scientific discipline only in the 1970s, with advances in laboratory technologies for isolating and characterizing DNA, RNA, proteins, and other small biological entities.
mood: A state of mind or feeling. In neuroscience, depression and anxiety are considered mood disorders, for example.
motor cortex: The part of the brain’s cerebrum, just to the front of the central sulcus in the frontal lobe, that is involved in movement and muscle coordination. Scientists have identified specific spots in the motor cortex that control movement in specific parts of the body, the so-called “motor map.”
multiple sclerosis: A progressive neurodegenerative disease involving damage to the protective myelin sheaths of nerve cells in the brain and spinal cord. Symptoms include impaired movement, pain, and fatigue.
mutation: A permanent structural alteration to DNA that modifies its previous nucleotide sequence. In most cases, DNA changes either have no effect or cause harm, but occasionally a mutation improves an organism’s chance of surviving and procreating.
myelin: The fatty substance that encases most nerve cell axons, helping to insulate and protect the nerve fiber and effectively speeding up the transmission of nerve impulses.
narcotic: A synthetic chemical compound that mimics the action of the body’s natural endorphins—hormones secreted to counteract pain. Narcotic drugs have a valid and useful role in the management of pain but may lead to physical dependence in susceptible individuals if used for long periods.
nerve growth factor: Also referred to as a neurotrophic factor, this special protein helps regulate the growth and survival of nerve cells. One of the most well-known of these is brain-derived neurotrophic factor (BDNF).
nerve cell: See neuron.
nerve impulse: Also referred to as a nerve signal, the way that a neuron communicates with other cells by transmitting an electrochemical signal down the length of the axon.
nervous system: The system in the body that processes and transmits signals from the brain to the rest of the body to facilitate movement and behavior. It consists of two parts, the central nervous system, or the brain and spinal cord, and the peripheral nervous system, the nerves that branch off from the spinal cord extending throughout the rest of the body.
neuroeconomics: An interdisciplinary field of study that uses neuroscientific research to help explain human decision-making behavior.
neurodegenerative diseases: Diseases characterized by the progressive deterioration and death of nerve cells (neurodegeneration), typically originating in one area of the brain and spreading to other connected areas. Neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), Huntington’s disease, Alzheimer’s disease, frontotemporal degeneration, and Parkinson’s disease.
neurodevelopmental disorder: Disorders or conditions arising from impairments during the development and maturation of the brain and/or nervous system. Neurodevelopmental disorders include schizophrenia and autism spectrum disorder.
neuroeducation: Sometimes referred to as educational neuroscience, this collaborative, interdisciplinary field of study uses findings in cognitive neuroscience to inform teaching and other educational practices.
neuroethics: An interdisciplinary field of study that addresses the ethical implications of our increased ability to understand and change the brain. Enhanced cognitive performance, life extension, the use of neuroscience in marketing, and many other issues are included in this ongoing social-scientific debate.
neurogenesis: The production of new, maturing neurons by neural stem and progenitor cells. Rapid and widespread neurogenesis obviously occurs in the fetal brain in humans and other animals, but neuroscientists long believed that neurogenesis essentially does not occur in the adult human brain. However, over the past two decades, research has shown that it does in fact occur in the dentate gyrus of the hippocampus and possibly other brain regions. This “adult neurogenesis” appears to be vital for normal learning and memory, and may help protect the brain against stress and depression.
neuroimmunology: A complex field in biomedical research, which focuses on the brain, the immune system, and their interactions. Neuroimmunology holds the potential for conquering ills as diverse as spinal cord injury, multiple sclerosis, and bodily reactions to bacteria or viruses, both naturally occurring and intentionally inflicted. In some circumstances, an abnormal neuroimmune response can damage brain tissue.
neuroplasticity: Also referred to as brain plasticity or neural plasticity, this is the ability of the brain to change throughout the lifespan, forming new synapses and neural connections in response to the environment.
neuron: A nerve cell. The basic unit of the central nervous system, the neuron is responsible for the transmission of nerve impulses. Unlike any other cell in the body, a neuron consists of a central cell body as well as several threadlike “arms” called axons and dendrites, which transmit nerve impulses. Scientists estimate that there are approximately 86 billion neurons in the human brain.
neuroscience: The study of the brain and nervous system, including their structure, function, and disorders. Neuroscience as an organized discipline gained great prominence in the latter part of the 20 th century.
neurotransmitter: A chemical that acts as a messenger between neurons and is released into the synaptic cleft when a nerve impulse reaches the end of an axon. Several dozen neurotransmitters have been identified in the brain so far, each with specific, often complex roles in brain function and human behavior.
neurotrophic factor: See nerve growth factor.
nucleotide: Sometimes referred to as a nucleic acid, these are the biological building blocks of DNA.
nucleotide sequence: A specific and ordered array of nucleotides that make up a specific genetic variant or allele.
nucleus accumbens: Part of the brain’s reward circuitry, or mesolimbic pathway, this small region in the midbrain releases dopamine in response to rewarding experiences.
nurture: A popular term for the influence of environmental factors on human development, such as the experiences one is exposed to in early life. The term is often used in the context of “nature versus nurture,” which relates to the interplay of “nature” (genetic or inherited, predetermined influences) and environmental, or experiential, forces.
obsessive compulsive disorder (OCD): A form of anxiety disorder characterized by unreasonable thoughts, or obsessions, which result in compulsive, repetitive behaviors.
occipital lobe: A part of the brain’s cerebrum, located at the rear of the brain, above the cerebellum. The occipital lobe is primarily concerned with vision and encompasses the visual cortex.
olfactory: Pertaining to the sense of smell. When stimulated by an odor, olfactory receptor cells in the nose send nerve impulses to the brain’s olfactory bulbs, which then transmit the impulses to olfactory centers in the brain for interpretation.
opiate: A synthetic (e.g., Demerol, Fentanyl) or plant-derived (e.g., opium, heroin, morphine) compound that binds and activates opioid receptors on certain neurons. Opiates typically but not always have pain-relieving, anxiety-reducing, and even euphoria-inducing effects, and are generally considered addictive.
opioid: An artificially derived drug or chemical that acts on the nervous system in a similar manner to opiates, influencing the “pleasure pathways” of the dopamine system by locking on to specialized opioid receptors in certain neurons.
opioid receptors (e.g., mu, delta, kappa): A class of receptors found on neurons in the brain, spinal cord, and digestive tract. Opioid receptors are involved in numerous functions, including pain control, mood, digestion, and breathing.
optic nerve: One of the twelve pairs of cranial nerves in the human body, the optic nerve transmits information from the retina, at the back of the eye, to the brain.
optogenetics: An innovative neuroscientific technique that uses light to turn genetically modified neurons on and off at will, in live animals.
oxytocin: Sometimes referred to as the “cuddle chemical,” this hormone can work as a neurotransmitter in the brain and has been linked to social attachment and parental care. While there are “love” sprays on the market that are said to contain oxytocin, there is no evidence that these concoctions have any effect on social relationships.
pain receptors: Specialized nerve fibers in the skin and on the surfaces of internal organs, which detect painful stimuli and send signals to the brain.
parietal lobe: The area of the brain’s cerebrum located just behind the central sulcus. It is concerned primarily with the reception and processing of sensory information from the body and is also involved in map interpretation and spatial orientation (recognizing one’s position in space in relation to other objects or places).
Parkinson’s disease: A neurodegenerative disorder characterized by tremor, slowed movement, and speech changes due to the death of dopamine neurons located in the substantia nigra.
perception: The way the brain organizes, processes, and interprets sensory information to give rise to our ability to make sense of and navigate the world around us.
peripheral nervous system: The nervous system outside the brain and spinal cord.
persistent vegetative state: A disorder of consciousness, often following severe brain trauma, in which an individual has not even minimal conscious awareness. The condition can be transient, marking a stage in recovery, or permanent.
pharmacotherapy: The use of pharmaceutical drugs for therapeutic purposes.
pituitary gland: An endocrine organ at the base of the brain that is closely linked with the hypothalamus. The pituitary gland is composed of two lobes, the anterior and posterior lobes, and secretes hormones that regulate the activity of the other endocrine organs in the body.
plasticity: In neuroscience, refers to the brain’s capacity to change and adapt in response to developmental forces, learning processes, injury, or aging.
positron emission tomography (PET): An imaging technique, often used in brain imaging. For a PET scan of the brain, a radioactive “marker” that emits, or releases, positrons (parts of an atom that release gamma radiation) is injected into the bloodstream. Detectors outside of the head can sense these “positron emissions,” which are then reconstructed using sophisticated computer programs to create computer images. Since blood flow and metabolism increase in brain regions at work, those areas have higher concentrations of the marker, and researchers can see which brain regions activate during certain tasks or exposure to sensory stimuli. Ligands can be added to a PET scan to detect pathological entities such as amyloid or tau deposits.
postsynaptic cell: The neuron on the receiving end of a nerve impulse transmitted from another neuron.
post-traumatic stress disorder (PTSD): A mental disorder that develops in response to a traumatic event such as combat, sexual assault, or abuse. Symptoms can include mood disturbances, hyperarousal, memory flashbacks, sleep problems, anxiety, and depression.
prefrontal cortex: The area of the cerebrum located in the forward part of the frontal lobe, which mediates many of the higher cognitive processes such as planning, reasoning, and “social cognition”—a complex skill involving the ability to assess social situations in light of previous experience and personal knowledge, and interact appropriately with others. The prefrontal cortex is thought to be the most recently evolved area of the brain.
premotor cortex: The area of the cerebrum located between the prefrontal cortex and the motor cortex, in the frontal lobe. It is involved in the planning and execution of movements.
presynaptic cell: In synaptic transmission, the neuron that sends a nerve impulse across the synaptic cleft to another neuron.
prion: A protein aggregate that can multiply itself, inducing the formation of new aggregates from individual copies of the protein it encounters. Prions have the potential to spread within the body and brain, and even from one organism to another—“infectiously,” like a virus. The first prions described were hardy aggregates of PrP, the prion protein. They are responsible for a set of rapid, fatal, and potentially transmissible neurodegenerative diseases including Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (“mad cow disease”). Many researchers now argue that protein aggregates in other neurodegenerative diseases, such as the Aβ and tau plaques of Alzheimer’s, have such similar properties that they also deserve to be called prions.
protein folding: The process by which the chain of amino acids that make up a protein assumes its functional shape. The protein clumps and tangles that occur in some neurodegenerative disorders are thought to be triggered when proteins “misfold.”
psychiatry: A medical specialty dealing with the diagnosis and treatment of mental disorders. Psychiatrists are physicians who can prescribe medicine and perform certain medical treatments. (Contrast with psychology)
psychoactive drug: A broad term to describe a drug that acts on the brain and changes one’s mental state, like elevating mood or reducing inhibitions. Psychoactive pharmaceuticals can help control the symptoms of some neurological and psychiatric disorders. Many “recreational drugs” are also psychoactive drugs.
psychological dependence: In the science of addiction, psychological dependence refers to the psychological factors, including mood and motivation that help to sustain addictive behaviors (like craving a cigarette after a meal), as opposed to the physical dependence that manifests when a person attempts to stop using a particular substance (e.g., tremors, racing pulse). Brain scientists now understand that psychological factors are central to addictive disorders and are often the most difficult to treat.
psychology: An academic or scientific field of study concerned with the behavior of humans and animals and related mental processes. Psychologists typically have Ph.D. degrees and while able to evaluate and treat mental disorders, are rarely able to prescribe medication. (Contrast with psychiatry)
psychosis: A severe symptom of mental illness in which a person’s thoughts and perceptions are so disordered that the individual loses touch with reality.
rapid eye movement (REM) sleep: A stage of sleep occurring approximately 90 minutes after sleep onset characterized by increased brain activity, rapid eye movements, and muscle relaxation.
receptors: Molecules on the surfaces of neurons whose structures precisely match those of chemical messengers (such as neurotransmitters or hormones) released during synaptic transmission. The chemicals attach themselves to the receptors, in lock-and-key fashion, to activate the receiving cell structure.
recessive: A genetic trait or disease that appears only in patients who have received two copies of a mutant gene, one from each parent.
recovery of function: The ability of the nervous system to repair or compensate for damage to the brain or nervous system after insult or injury in order to regain function. For example, after a stroke, many individuals must learn how to walk or talk again.
rehabilitation: The process by which people can repair, recover, or compensate for functional abilities after sustaining damage to the nervous system. Rehabilitation activities may include speech, physical, or occupational therapies.
resting state: The state of the brain when it is not consciously engaged in an explicit task. Brain imaging techniques such as fMRI can be used to measure the residual activity that occurs in this state.
retina: The sensory membrane at the back of the eye that processes light information to facilitate sight.
reward/reinforcement brain network: Also known as the mesolimbic circuit, this important network of brain regions stretching from the brain stem to the frontal lobes is implicated in risk and reward processing, as well as learning.
reuptake: A process by which released neurotransmitters are absorbed for subsequent re-use.
RNA (ribonucleic acid): A chemical similar to a single strand of DNA. The sugar is ribose, not deoxyribose, hence RNA. RNA delivers DNA’s genetic message to the cytoplasm of a cell, where proteins are made.
rod: A type of photoreceptor, usually found on the outer edges of the retina, that helps facilitate peripheral vision.
High-speed microscope captures fleeting brain signals
Electrical and chemical signals flash through our brains constantly as we move through the world, but it would take a high-speed camera and a window into the brain to capture their fleeting paths.
University of California, Berkeley, investigators have now built such a camera: a microscope that can image the brain of an alert mouse 1,000 times a second, recording for the first time the passage of millisecond electrical pulses through neurons.
“This is really exciting, because we are now able to do something that people really weren’t able to do before,” said lead researcher Na Ji, a UC Berkeley associate professor of physics and of molecular and cell biology.
The new imaging technique combines two-photon fluorescence microscopy and all-optical laser scanning in a state-of-the-art microscope that can image a two-dimensional slice through the neocortex of the mouse brain up to 3,000 times per second. That’s fast enough to trace electrical signals flowing through brain circuits.
With this technique, neuroscientists like Ji can now clock electrical signals as they propagate through the brain and ultimately look for transmission problems associated with disease.
One key advantage of the technique is that it will allow neuroscientists to track the hundreds to tens of thousands of inputs any given brain cell receives from other brain cells, including those that don’t trigger the cell to fire. These sub-threshold inputs — either exciting or inhibiting the neuron — gradually add up to a crescendo that triggers the cell to fire an action potential, passing information along to other neurons.
From electrodes to fluorescence imaging
The typical method for recording electrical firing in the brain, via electrodes embedded in the tissue, detects only blips from a few neurons as the millisecond voltage changes pass by. The new technique can pinpoint the actual firing neuron and follow the path of the signal, millisecond by millisecond.
Rapid imaging – a thousand times per second — shows spontaneous electrical activity in four separate neurons 75 micron inside the brain of an alert mouse. This is a 3-micron-thick slice through the neocortex – so thin that the cell body of the neuron is seen only in cross section, as a circle. (UC Berkeley image by Na Ji)
“In diseases, many things are happening, even before you can see neurons firing, like all the subthreshold events,” said Ji, a member of UC Berkeley’s Helen Wills Neuroscience Institute. “We’ve never looked at how a disease will change with subthreshold input. Now, we have a handle to address that.”
Ji and her colleagues reported the new imaging technique in the March issue of the journal Nature Methods. In the same issue, she and other colleagues also published a paper demonstrating a different technique for imaging calcium signaling over much of an entire hemisphere of the mouse brain at once, one that uses a wide-field-of-view “mesoscope” with two-photon imaging and Bessel focus scanning. Calcium concentrations are linked with voltage changes as signals are transmitted through the brain.
“This is the first time anyone has shown in three dimensions the neural activity of such a large volume of the brain at once, which is far beyond what electrodes can do,” Ji said. “Furthermore, our imaging approach gives us the ability to resolve the synapses of each neuron.”
Synapses are the spots where neurotransmitters are released by one neuron to excite or inhibit another.
One of Ji’s goals is to understand how neurons interact across large areas of the brain and eventually locate diseased circuits linked to brain disorders.
“In brain disorders, including neurodegenerative disease, it’s not just a single neuron or a few neurons that get sick,” Ji said. “So, if you really want to understand these illnesses, you want to be able to look at as many neurons as possible over different brain regions. With this method, we can get a much more global picture of what is happening in the brain.”
Ji and her colleagues are able to peer into the brain thanks to probes that can be pinned to specific types of cells and become fluorescent when the environment changes. To track voltage changes in neurons, for example, her team employed a sensor developed by co-author Michael Lin of Stanford University that becomes fluorescent when the cell membrane depolarizes as a voltage signal propagates along the cell membrane.
Using a two-photon fluorescence microscope with an extra-large field of view, UC Berkeley researchers imaged neurons (green) in a large chunk of the cortex of the brain of a living mouse. The area shows neurites in a volume of 4.2 mm × 4.2 mm x 100 microns. The dark branches are blood vessels. (UC Berkeley image by Na Ji)
The researchers then illuminate these fluorescent probes with a two-photon laser, which makes them emit light, or fluoresce, if they have been activated. The emitted light is captured by a microscope and combined into a 2D image that shows the location of the voltage change or the presence of a specific chemical, such as the signaling ion, calcium.
By rapidly scanning the laser over the brain, much like a flashlight that gradually reveals the scene inside a darkened room, researchers are able to obtain images of a single, thin layer of the neocortex. The team was able to conduct 1,000 to 3,000 full 2D scans of a single brain layer every second by replacing one of the laser’s two rotating mirrors with an optical mirror — a technique called free-space angular-chirp-enhanced delay (FACED). FACED was developed by paper co-author Kevin Tsia at the University of Hong Kong.
The kilohertz imaging not only revealed millisecond changes in voltage, but also more slowly changing concentrations of calcium and glutamate, a neurotransmitter, as deep as 350 microns (one-third of a millimeter) from the brain’s surface.
To obtain rapid 3D images of the movement of calcium through neurons, she combined two-photon fluorescent microscopy with a different technique, Bessel focus scanning. To avoid time-consuming scans of every micron-thick layer of the neocortex, the excitation focus of the two-photon laser is shaped from a point to a small cylinder, like a pencil, about 100 microns in length. This pencil beam is then scanned at six different depths through the brain, and the fluorescent images are combined to create a 3D image. This allows more rapid scanning with little loss of information because in each pencil-like volume, typically only one neuron is active at any time. The mesoscope can image an area about 5 mm in diameter — nearly a quarter of one hemisphere of the mouse brain — and 650 microns deep, close to the full depth of the neocortex, which is involved in complex information processing.
“Using conventional methods, we would have to scan 300 images to cover this volume, but with an elongated beam that collapses the volume onto a single plane, we only need to scan six images, which means that now we can have a fast enough volumetric rate to look at its calcium activity,” Ji said.
Ji is now working on combining four techniques — two-photon fluorescence microscopy, Bessel beam focusing, FACED and adaptive optics — to achieve high-speed, high sensitivity images deep in the neocortex, which is about 1 millimeter thick.
“As a way to understand the brain, my dream is to combine these microscopy techniques to get submicron spatial resolution so we can see the synapses, millisecond time resolution for the voltage imaging, and see all of this deep in the brain,” she added. “What is complicated and challenging about the brain is that, if you only do one single optical section, in a way you don’t get a complete picture, because a neural network is very much three-dimensional.”
Co-authors on the voltage imaging paper with Ji, Lin and Tsia are Jianglai Wu and Shuo Chen of UC Berkeley, Yajie Liang and Ching-Lung Hsu of the Howard Hughes Medical Institute (HHMI) Janelia Research Campus in Virginia, and Mariya Chavarha, Stephen Evans and Dongqing Shi of Stanford.
Co-authors with Ji on the calcium imaging paper are co-first authors Rongwen Lu and Yajie Liang of Janelia and Guanghan Meng of UC Berkeley Pengcheng Zhou and Liam Paninski of Columbia University and Karel Svoboda of Janelia.
Ji’s work is supported by HHMI and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (U01NS103489, UF1NS107696).